Abstract
Estrogen is the natural agonist of the estrogen receptor (ER). However, certain plant-derived compounds or phytoestrogens have been identified that mimic estrogens and act as agonists and/or antagonists of ERs, depending on subtype and target tissue. Using thin layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS), and proton nuclear magnetic resonance (1H-NMR), we identified a simple phenol, 4-ethoxymethylphenol (4EM), found in Maclura pomifera that acts as an agonist of ER-α and ER-β in HeLa and MCF-7 cells. To study the effect of 4EM on ER-α and ER-β activity, we performed transient transfection assays and showed that 4EM activated ER-dependent gene transcription in a dose-dependent manner on both ER subtypes and this activity was inhibited by trans-4-hydroxytamoxifen (4HT). Further, 4EM-mediated transcription in ER-α, like estrogen, was enhanced in the presence of coactivators, steroid receptor coactivator-1 (SRC-1), CREB binding proteins (CBP), and E6-associated protein (E6-AP). We found that 4EM was specific for ER and did not activate transcription of the progesterone receptor.
| Original language | English |
|---|---|
| Pages (from-to) | 431-439 |
| Number of pages | 9 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 84 |
| Issue number | 4 |
| DOIs | |
| State | Published - Mar 1 2003 |
| Externally published | Yes |
Fingerprint
Keywords
- 4-Ethoxymethylphenol
- 4HT
- Agonist
- CBP
- Coactivators
- E6-AP
- ER-α
- ER-β
- Estrogen
- Estrogen receptor
- Maclura pomifera
- Phytoestrogens
- Progesterone receptor
- SRC-1
- Tamoxifen
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
Cite this
4-Ethoxymethylphenol : A novel phytoestrogen that acts as an agonist for human estrogen receptors. / Pearce, Virginia; Nawaz, Zafar; Xiao, Wu; Wiedenfeld, David; Boyle, Nick; Smith, Don.
In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 84, No. 4, 01.03.2003, p. 431-439.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 4-Ethoxymethylphenol
T2 - A novel phytoestrogen that acts as an agonist for human estrogen receptors
AU - Pearce, Virginia
AU - Nawaz, Zafar
AU - Xiao, Wu
AU - Wiedenfeld, David
AU - Boyle, Nick
AU - Smith, Don
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Estrogen is the natural agonist of the estrogen receptor (ER). However, certain plant-derived compounds or phytoestrogens have been identified that mimic estrogens and act as agonists and/or antagonists of ERs, depending on subtype and target tissue. Using thin layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS), and proton nuclear magnetic resonance (1H-NMR), we identified a simple phenol, 4-ethoxymethylphenol (4EM), found in Maclura pomifera that acts as an agonist of ER-α and ER-β in HeLa and MCF-7 cells. To study the effect of 4EM on ER-α and ER-β activity, we performed transient transfection assays and showed that 4EM activated ER-dependent gene transcription in a dose-dependent manner on both ER subtypes and this activity was inhibited by trans-4-hydroxytamoxifen (4HT). Further, 4EM-mediated transcription in ER-α, like estrogen, was enhanced in the presence of coactivators, steroid receptor coactivator-1 (SRC-1), CREB binding proteins (CBP), and E6-associated protein (E6-AP). We found that 4EM was specific for ER and did not activate transcription of the progesterone receptor.
AB - Estrogen is the natural agonist of the estrogen receptor (ER). However, certain plant-derived compounds or phytoestrogens have been identified that mimic estrogens and act as agonists and/or antagonists of ERs, depending on subtype and target tissue. Using thin layer chromatography (TLC), gas chromatography-mass spectrometry (GC-MS), and proton nuclear magnetic resonance (1H-NMR), we identified a simple phenol, 4-ethoxymethylphenol (4EM), found in Maclura pomifera that acts as an agonist of ER-α and ER-β in HeLa and MCF-7 cells. To study the effect of 4EM on ER-α and ER-β activity, we performed transient transfection assays and showed that 4EM activated ER-dependent gene transcription in a dose-dependent manner on both ER subtypes and this activity was inhibited by trans-4-hydroxytamoxifen (4HT). Further, 4EM-mediated transcription in ER-α, like estrogen, was enhanced in the presence of coactivators, steroid receptor coactivator-1 (SRC-1), CREB binding proteins (CBP), and E6-associated protein (E6-AP). We found that 4EM was specific for ER and did not activate transcription of the progesterone receptor.
KW - 4-Ethoxymethylphenol
KW - 4HT
KW - Agonist
KW - CBP
KW - Coactivators
KW - E6-AP
KW - ER-α
KW - ER-β
KW - Estrogen
KW - Estrogen receptor
KW - Maclura pomifera
KW - Phytoestrogens
KW - Progesterone receptor
KW - SRC-1
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=0038556693&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038556693&partnerID=8YFLogxK
U2 - 10.1016/S0960-0760(03)00064-5
DO - 10.1016/S0960-0760(03)00064-5
M3 - Article
C2 - 12732288
AN - SCOPUS:0038556693
VL - 84
SP - 431
EP - 439
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
IS - 4
ER -